Retinopathy of Prematurity (ROP) remains a serious public health problem causing significant visual sequelae in an estimated 3400 premature infant survivors per year in the United States, despite the use of cryotherapy. Case control studies in premature infants, anecdotal reports of successful treatment of ROP with oxygen, and studies conducted in experimental models demonstrate that chronic (weeks-long) hypoxia during the healing process is associated with retinopathy that progresses rather than regresses. This hypothesis is supported by association of proliferative retinopathies with retinal ischemia in other disorders such as diabetic or sickle cell retinopathies. We proposed to test the hypothesis that: "Supplemental Oxygen Treatment of Prethreshold R0P will result in a reduction by at least one third in the number of infants with one or both eyes progressing to severe ROP (Threshold)." Infants who develop moderate ROP (Prethreshold) will receive continuous pulse oximetry saturation monitoring and be randomly assigned to oxygen administration at one of two specified oxygen levels: conventional vs supplemental. Their ROP status will be measured and recorded prospectively. The primary outcome variable will be the proportion of infants who progress to Threshold ROP in at least one eye. Follow-up will continue three months following the projected time of full term delivery. Projected sample sizes are compatible with a 2-3 year enrollment with 20- 30 participating centers. This proposal requests support for New England Medical Center (NEMC) as a Participating Center in Supplemental Therapeutic Oxygen for Prethreshold Retinopathy of Prematurity (ST0P-R0P) Study. Subjects will be enrolled in the two neonatal intensive care units (NICUs) associated with the Boston Perinatal Center (BPC) at NEMC and Boston City Hospital (BCH). NEMC is the primary applicant, and participation of BCH is through a subcontract. With expansion in the NEMC and BCH high-risk obstetric services in 1992, the BPC will be able to recruit a projected minimum of 16 eligible infants per year (10 from NEMC, 6 from BCH). The close ophthalmologic and neonatal collaboration, and the previous experience of personnel and nursing staff with multicenter clinical trials supports the ability of the BPC to contribute to the success of STOP-ROP. BPC through NEMC and BCH will participate with Study Headquarters in Rochester, New York and Coordinating Center at EMMES Corporation in Maryland, and will comply with study design and Manual of Procedures (submitted separately by Headquarters and Coordinating Center).